By 2050, antimicrobial resistance will be responsible for 300 million deaths and drain up to $100 trillion from the world's GDP. While the dwindling antibiotic pipeline has been well documented, a less obvious threat is attrition of the field's research workforce. To confront this looming threat, it is essential to identify, nurture, and prepare the next generation of clinician-scientists pursuing patient-oriented research (POR) on antibiotic-resistant bacteria. In this competitive renewal of my K24, I will do precisely that. The overarching goal of this K24 competitive renewal is to further develop my mentoring and leadership skills by training the next generation of clinician-scientists in clinical and translational POR of antibiotic-resistant bacteria. My original K24 supported me to mentor clinical and translational patient oriented research in staphylococci. It was highly successful. Trainees received extramural funding and published over 30 1st author manuscripts, including one that was identified as being one of the top 10 Clinical Research Achievements in the United States for the year by the Clinical Research Forum. In this competitive renewal, I will expand the focus of my mentoring platform to include Gram-negative bacilli, antibiotic stewardship, and innovative clinical trials. To do this, I will leverage unique resources that I assembled during th initial cycle of this K24: the Antibacterial Resistance Leadership Group (ARLG) and the Blood Stream Infection Biorepository (BSIB). Begun in May, 2013, the ARLG (https://arlg.org/) is a $65 million grant to identify, prioritize, design, and execute clinical research in antibiotic-resistan bacteria. As corresponding PI of the ARLG, my vision is to leverage this infrastructure to advance the careers of young investigators from both Duke University and throughout the United States. I created the BSIB with funds from the original K24 to support the research of my trainees. It contains the infecting bacterial isolate and human DNA, RNA, and serum from >2000 prospectively characterized patients with Gram-negative bacteremia. Mentoring skills are not innate; they can and should be learned. Thus, I will continue to develop my mentoring expertise in several ways. First, I will complete the Leadership Program of the Duke Fuqua School of Business. Second, I will meet weekly for a year with an executive coach to review my mentoring and leadership interactions. Finally, I will receive regular review from an Advisory Board of senior researchers and leaders. Scientifically, I will facilitate my mentoring plan by pursuing two Specific Aims that incorporate the breadth of my research platform. These Specific Aims are supported by a total of 8 distinct projects, each of which is assigned to a trainee. Some of these projects are current research, while others are new research specifically supported by the K24. These projects will serve as the hypothesis-testing science that undergirds my mentoring plan. Specific Aim 1, mentoring clinical POR in antibiotic-resistant bacteria, will be accomplished by pursuing 4 individual projects. One of these projects focuses on a large, NIH-funded, multinational trial of staphylococcal bacteremia, two projects are funded by ARLG to evaluate issues involving antibiotic stewardship, and the last is a large, FDA-funded project to evaluate improvements in clinical trial design in the area of Hospital-acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia. Specific Aim 2, mentoring translational patient-oriented research in antibiotic-resistant bacteria, will be accomplished by pursuing four projects involving bacterial and host genetic determinants of antibiotic-resistant bacteria. Two of these projects are new research funded solely by my K24. My long-term objective is to create a multidisciplinary program that focuses on clinical and translational POR of antibiotic-resistant bacteria. By expanding the breadth of my research program, the competitive renewal of my K24 would enhance my progress toward this goal, and would help to prepare the next generation of clinician-scientists to confront antibiotic-resistant bacteria.